4-Methoxybenzenesulfonyl chloride → N-(tetrahydro-2H-pyran-4-yloxy)-4-methoxy-1-benzenesulfonamide

HRID 29163Notes

Reaction equation

HRID 29163 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][N:8]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:3][CH2:2]1.NN.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>C1COCC1>[O:1]1[CH2:2][CH2:3][CH:4]([O:7][NH:8][S:29]([C:26]2[CH:25]=[CH:24][C:23]([O:22][CH3:21])=[CH:28][CH:27]=2)(=[O:31])=[O:30])[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 229971882-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 22997150N-(tetrahydro-2H-pyran-4-yloxy)-4-methoxy-1-benzenesulfonamideYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione (6.8 mmol, 1.69 g) was combined with hydrazine (6.8 mmol, 0.22 mL) in anhydrous THF (20 mL) under nitrogen. The reaction immediately formed a white suspension and was allowed to stir at room temperature for 1 hour. The suspension was filtered directly into a flask containing 4-methoxybenzenesulfonyl chloride (6.5 mmol, 1.34 g) and diisopropylethylamine (20.5 mmol, 3.6 mL) was added. After stirring at room temperature for 15 hours, the reaction was refluxed for 4 hours, then stirred at room temperature for 12 days and concentrated to a yellow solid. The resulting solid was partitioned between ethyl acetate and 1N HCl, and the organic layer was separated and washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried over magnesium sulfate. The crude product was concentrated to a white solid and purified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization (hexanes/ethyl acetate) providing 0.554 g (30%) of a white solid. Rf=0.4 (1:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.83(2H,d), 7.00 (2H,d), 6.72 (1H,s), 4.23-4.11 (1H,m), 3.91-3.81 (2H,m), 3.87 (3H,s), 3.46-3.38 (2H,m), 2.03-1.94 (2H,m), 1.63-1.51 (2H,m).

Workup

  1. customThe reaction
  2. customimmediately formed a white suspension
  3. filtrationThe suspension was filtered directly into a flask
  4. additionwas added
  5. stirringAfter stirring at room temperature for 15 hours
  6. temperaturethe reaction was refluxed for 4 hours
  7. stirringstirred at room temperature for 12 days
  8. concentrationconcentrated to a yellow solid
  9. customThe resulting solid was partitioned between ethyl acetate and 1N HCl
  10. customthe organic layer was separated
  11. washwashed with a saturated aqueous solution of sodium bicarbonate and brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationThe crude product was concentrated to a white solid
  14. custompurified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-feca94a4b9b2431c85e824c50b71deef
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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